Article Figures & Data
Tables
- Table 1
- Registered liver transplantation in the Kingdom of Saudi Arabia between 2018 and 2019.
Country LDLT 2018 DDLT 2018 LDLT 2019 DDLT 2019 Split 2018 Split 2019 Saudi Arabia 207 62 241 78 0 4 - Table 2
- Grading of Recommendations Assessment Development and Evaluation (GRADE) system used in the Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia.
GRADE evidence I Randomized, controlled trials II-1 Controlled trials without randomization II-2 Cohort or case-control analytic studies II-3 Multiple time series, dramatic uncontrolled experiments III Opinions of respected authorities, descriptive epidemiology - Table 3
- Risk stratification of microbial transmission from donor to recipient in liver transplantation (LT).
Risk classification Description Unacceptable risk Diseases with no definitive treatment, such as HIV, MDR bacterial infections, and some viral CNS infections. Encephalitis without proven cause falls in this category, as well as active tuberculosis Increased but acceptable risk Justified by the severity of the recipient condition and risk of death. Examples are HCV and HBV in the donor. Calculated risk When recipients have the same disease as the donor or in cases where the infection can be mitigated by antibiotics, such as septicemia and bacterial meningitis. Non-assessable risk When the risk cannot be estimated based on donor data, such as organs from donors with highly resistant bacteria or fungal infection. The use of these organs should be avoided. Standard risk Donors whose evaluation did not reveal transmissible disease. HIV: human immunodeficiency virus, MDR: multi drug-resistant, HCV: hepatitis C virus
- Table 4
- Management of infectious complications in liver transplantation (LT) listed patients.
Infectious Complication Evidence Recommendations UTI • Almost 90% of nosocomial UTIs are mainly Foley catheter-related and can precipitate to AKI • Insertion of Foley catheters in patients should only be used when absolutely indicated SBP • SBP is a common precipitant of AKI and encephalopathy and often complicates gastrointestinal hemorrhage. • All hospitalized patients with cirrhosis and ascites should undergo diagnostic paracentesis to rule out SBP at admission or if clinical deterioration occurs. • Nosocomial SBP is more often MDR, more frequently caused by gram-positive organisms, and has up to 50% mortality. • Primary prophylaxis in patients: with ascitic fluid total protein, <1.5 g/dL; CTP score 9 and serum bilirubin, 3 mg/dL or renal impairment (sCr, 1.2 mg/dL; serum blood urea nitrogen, 25; or serum Na, 130) • Secondary SBP prophylaxis is always indicated. • The drug of choice for the prophylaxis is norfloxacin or, if not available, daily ciprofloxacin or trimethoprim/sulfamethoxazole would be the preferred substitution. • Piperacillin/tazobactam or meropenem is recommended during SBP infection, and patients should receive intravenous albumin to prevent HRS Clostridium difficile colitis • Incidence and severity is increasing in hospitalized patients, directly related to liver disease as well as other modifiable risk factors namely, SBP antibiotic prophylaxis, other antibiotic use, and PPI use • Low-risk patients can safely receive metronidazole, but patients with severe diseases require the use of either oral vancomycin or fidaxomicin Pneumonia • Usually precipitated by multiple risk factors: • Pneumonia must always be distinguished from volume overload and atelectasis • Hepatic encephalopathy and gastrointestinal bleeding both increase the risk of aspiration • Use of PPIs increases gastrointestinal flora growth • Ascites increase intra-abdominal pressure that can result in atelectasis UTI: urinary tract infection, AKI: acute kidney injury, SBP: spontaneous bacterial peritonitis, MDR: multi drug-resistant, PPI: proton pump inhibitor, CTP: Child-Turcotte-Pugh, sCR: serum creatinine, HRS: hepatorenal syndrome
Non-infectious complication Clinical outcome Recommendations Variceal bleeding • 20% initial risk of death
• Primary and secondary variceal hemorrhage prophylaxis is the standard of care for prevention.
• Primary prophylaxis depends on the MELD score• Carvedilol leads to a greater hemodynamic response than NSBB because of its alpha-adrenergic blockade, but this can worsen fluid accumulation
• Hyponatremia should be avoided in high MELD patients.
• NSBB will be a better option, but it should be avoided in patients with refractory ascites after SBP development, and those who require variceal band ligation
• Secondary prophylaxis with endoscopic banding to obliteration and NSBB/carvedilol, both modalities, if tolerated, are standard of careRenal failure • Renal dysfunction typically implies a substantially increased risk of mortality, commonly precipitated by a bacterial infection, then hypovolemia.
• Other etiologies include HRS and parenchymal nephropathy.• Identify and treat infection with antibiotic therapy.
• Appropriate prophylactic antibiotic therapy should be used in variceal hemorrhage or SBP prophylaxis.
• Antibiotic therapy administration should be used when an infection is suspected, and hypovolemia is treated.
• Avoid overdosing lactulose, intravenous albumin administration when SBP occurs.
• Withdraw diuretics and nephrotoxic drugs.
• Vasoconstrictor medications are used to correct peripheral vasodilatation if HRS is suspected.
• Midodrine, in combination with octreotide or terlipressin, is suggested, which does not require ICU monitoringRefractory ascites and HH • Ascites is the most common complication of cirrhosis that leads to hospital admission.
• 50% of patients with compensated cirrhosis develop ascites over ten years, and 15% and 44% of patients will die in one and five years, respectively.
• HH is a complication seen in approximately 5-16% of patients with cirrhosis, usually with ascites.• Initial management, both with diuretics and sodium restriction, should be effective in 10-20% of cases.
• Predictors of response are mild or moderate ascites/HH, especially with urine Na+ excretion >78 mEq/day.
• Spironolactone-based diuretics can be used and then add lop diuretics e.g. furosemide (1:4 ratio to preserve potassium).
• In an intractable/recurrent ascites/HH, paracentesis and thoracentesis are often needed to optimize ventilator management and to help treat or prevent pneumonia during hospitalization.
• TIPS is a good option in low MELD patients, but contraindicated in high MELD patientsHepatic encephalopathy • Precipitated by infection, dehydration, gastrointestinal bleeding, worsening hepatic function, TIPS placement, hypokalemia, hyponatremia, and numerous medications • HE is prevented by avoiding dehydration and electrolyte optimization, specifically potassium repletion to avoid increased renal ammonia-genesis in the presence of hypokalemia, and avoidance of starvation.
• Treatment options include: lactulose, rifaximin, sodium benzoate and polyethylene glycol
• Replacement of benzodiazepine-derived sleep-aids with diphenhydramine, melatonin, or trazodone can also work.
• Patients with TIPS who continue to experience refractory encephalopathy may need their TIPS downsized.Hyponatremia • Low serum Na levels reflect the intensity of portal hypertension, and is associated with ascites and HRS.
Serum Na+ <126 mEq/L at the time of listing is associated with poor outcomes.
• The need for intervention in dilutional hyponatremia is dictated by the absolute serum Na level, the rapidity of decrease, and the presence or absence of symptoms.In asymptomatic patients, fluid restriction and limiting diuretic use are considered first-line interventions.
• In symptomatic patients, serum Na should be corrected slowly; a correction of <10 mEq/L to 12 mEq/L in 24 hours and <18 mEq/L in 48 hours is recommended.
• Vasopressin receptor antagonists (tolvaptan) remain an effective means of hyponatremia treatment when other therapeutic measures fail, and the risks have been consideredMELD: Model of End-stage Liver Disease, HRS: hepatorenal syndrome, HH: hereditary hemochromatosis, TIPS: Transjugular Intrahepatic Portosystemic Shunt, NSBB: Non selective Beta Blocker, SBP: Spontaneous Bacterial Peritonitis
Indications Disease Chronic liver disease Progressive familial intrahepatic
cholestasis (all types)
Biliary atresia
Autoimmune hepatitis
Sclerosing cholangitis
Caroli syndrome
Wilson’s disease
Cystic fibrosis
Alagille syndrome
Glycogen storage diseases type 1a, 3 and 4
Tight Junction Protein Type 2 (TJP2)
Bile acid coenzyme A: amino acid
N-acyltransferase (BAAT)
Tyrosinemia type 1
Alpha-1-antitrypsin deficiencyAcute liver failure - Liver tumors - Unresectable hepatoblastoma (without active extrahepatic disease) - Metabolic liver disease with life-threatening extrahepatic complications Crigler Najjar Syndrome
Urea cycle defects
Hypercholesterolemia
Organic acidemias
Primary hyperoxaluriaAntimicrobials Calcineurin inhibitors Mammalian target of rapamycin inhibitors Mycophenolate Fluoroquinolones (primarily ofloxacin > ciprofloxacin) Increased levels - - Macrolides (erythromycin > clarithromycin > azithromycin) Markedly increased levels Markedly increased levels - Rifamycins (rifampin > rifabutin) Markedly decreased levels Markedly decreased levels - Linezolid Increased myelosuppression Increased myelosuppression and platelet decrease Triazoles (ketoconazole / voriconazole / posaconazole > itraconazole / fluconazole) Increased levels Increased levels (voriconazole contraindicated) - Ganciclovir / valganciclovir Increased myelosuppression Increased myelosuppression - Table 8
- Prevalence of cardiovascular risk factors and CKD in LT recipients beyond the first post-transplant year.
Risk factors Prevalence rate % Cardiovascular risk factor
Metabolic syndrome*
Systemic hypertension
Diabetes mellitus
Obesity
Dyslipidemia
Cigarette smoking50 - 60
40 - 85
10 - 64
24 - 64
40 - 66
10 - 40CKD (stage 3-4)† 30-8 End-stage kidney disease 05-8 * Any 3 of the following: hypertension, obesity, dyslipidemia, and diabetes mellitus.
† Estimated glomerular filtration rate = 15 to <60 mL/minute/1.73 m2.
First month after LT 2-6 months after LT > 6 months after LT Nosocomial infections related to surgery and postoperative care Opportunistic infections Reactivation of latent infections Community-acquired infections Organism Drug/Dosage Duration Comments CMV Donor-positive/recipient-negative Valganciclovir (900 mg/day) or intravenous ganciclovir (5 mg/kg/day) 3-6 months Valganciclovir is not FDA-approved for LT. Prolonged-duration regimens are effective in kidney transplantation. Recipient-positive Valganciclovir (900 mg/day), intravenous ganciclovir, or weekly CMV viral load monitoring and antiviral initiation when viremia is identified 3 months Valganciclovir is not FDA-approved for LT. Fungi Fluconazole (100-400 mg daily), itraconazole (200 mg twice daily), caspofungin (50 mg daily), or liposomal amphotericin (1 mg/kg/day) 4-6 weeks (adjust duration) Reserve for high-risk individuals (pretransplant fungal colonization, renal replacement therapy, massive transfusion, choledochojejunostomy, re-operation, re-transplantation, or hepatic iron overload). P. jirovecii (P. carinii) Trimethoprim sulfamethoxazole (single strength daily or double strength 3 times per week), dapsone (100 mg daily), or atovaquone (1500 mg daily) 6-12 months (adjust duration) A longer duration of therapy should be considered for patients on augmented immunosuppression. Lifelong therapy should be considered for HIV-infected recipients. TB (latent infection) Isoniazid (300 mg daily) 9 months Monitor for hepatotoxicity
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- Abstract
- The need for Saudi Practice Guidelines
- 1. Organ Donation
- 2. Evaluation of an adult for liver transplant
- 3. Scoring system used to list patients for liver transplantation and managing patient complications while on the waitlist
- 4. Pediatric liver transplantation
- 5. Liver transplantation - Surgical aspects in adults and pediatrics
- 6. Post-transplant care
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